title: Structure and plasticity of Endophilin and Sorting Nexin 9.
abstract: Endophilin and Sorting Nexin 9 (Snx9) play key roles in endocytosis by membrane curvature sensing and remodeling via their Bin/Amphiphysin/Rvs (BAR) domains. BAR and the related F-BAR domains form dimeric, crescent-shaped units that occur N- or C-terminally to other lipid-binding, adaptor, or catalytic modules. In crystal structures, the PX-BAR unit of Snx9 (Snx9(PX-BAR)) adopts an overall compact, moderately curved conformation. SAXS-based solution studies revealed an alternative, more curved state of Snx9(PX-BAR) in which the PX domains are flexibly connected to the BAR domains, providing a model for how Snx9 exhibits lipid-dependent curvature preferences. In contrast, Endophilin appears to be rigid in solution, and the SH3 domains are located at the distal tips of a BAR domain dimer with fixed curvature. We also observed tip-to-tip interactions between the BAR domains in a trigonal crystal form of Snx9(PX-BAR) reminiscent of functionally important interactions described for F-BAR domains.
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Hung Yi Kristal
authors.initials: HY
authors.lastname: Kaan
authors.forename: Reshma Noordin
authors.initials: RN
authors.lastname: Hooda
authors.forename: Shih Lin
authors.initials: SL
authors.lastname: Goh
authors.forename: Holger
authors.initials: H
authors.lastname: Sondermann
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D053838:Scattering, Small Angle; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C400533:SNX9 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; C504641:endophilin A1 protein, mouse